[Monoclonal gammopathies associated with silicosis].
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Biomedical subjects
Publications and source records attributed to M Yasuda.
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The normal development of preterm rat fetuses (day 19.0 to day 21.0) was investigated with respect to body weight and ossification of the sacrococcygeal vertebrae, supraoccipital bone, sternebrae, and proximal phalanges in the forepaw. Normal standard growth curves were established for these indexes in rat fetuses. A method was devised for the analysis of the relationship between low body weight and retarded ossification induced by teratogenic agents. In normal fetuses, mean body weight and number of ossified sacrococcygeal vertebrae and the ossification stage of the supraoccipital bone increased approximately linearly with advancing fetal age. The number of ossified sternebrae and proximal phalanges in the forepaw increased curvilinearly with advancing fetal age. By use of the standard curves, fetal growth retardation observed in teratological experiments may be expressed as retardation in relation to the standard in hours. The characteristic pattern of growth retardation induced by an agent may be evaluated by comparison of the degree of retardation expressed in a common "hour" scale among various growth indexes. This method was applied to experimental data of fetal growth retardation induced by maternal fasting. The degree of retardation was found to differ among growth indexes; body weight and ossification of the sacrococcygeal vertebrae were the most severely retarded; ossification of the supraoccipital bone and the sternebrae was moderately retarded; ossification of the proximal phalanges in the forepaw was least retarded.
DPG-3-2, a component of ginseng radix, which lowers the blood glucose level and stimulates insulin release in diabetic animals, was studied for its effects on insulin biosynthesis in different preparations of pancreas from animals with normoglycemia and with hyperglycemia (alloxan diabetic rats and genetically diabetic mice, KK-CAy). We measured incorporation of radioactive leucine into insulin and other protein fractions during a 2-h perfusion of rat pancreas, and into insulin during a 3-h incubation of mouse islets. Biosynthesis of insulin during a long-term culture of islets from KK-CAy mice was also measured. DPG-3-2 was found practically not to increase the incorporation into insulin in the pancreatic preparations from animals with normoglycemia, but in such preparations from animals with hyperglycemia DPG-3-2 (0.2-1.0 mg/ml) caused 1.5-1.8-fold incorporation into insulin. In addition, a long-term treatment of DPG-3-2 (0.5 mg/ml) was shown to stimulate insulin biosynthesis in islets from KK-CAy mice. Ginsenoside-Rb1 and -Rg1 decreased the insulin content of islet to the undetectable level. Thus, DPG-3-2 was shown to stimulate insulin biosynthesis in different preparations of pancreas from animals with hyperglycemia.
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The following trial was conducted as a fundamental study in the application of piperacillin (PIPC) in the field of obstetrics and gynecology. A dose of 1 g was administered to 10 patients by intravenous injection and the concentrations of PIPC in the serum and the various tissues of the uterus were measured. This data was analyzed by the computer. 1. These concentrations were analyzed based on a two- or three-compartment model. We obtained the pharmacokinetic parameters and described the simulation curves. Correspondence was observed between the calculated and the actually determined concentrations. 2. PIPC was rapidly distributed to the tissues of the uterus and exhibited high concentrations. Transfer to these tissues correlated well with serum concentrations.
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The distribution of bacterial L-ornithine: alpha-ketoglutarate delta-aminotransferase (L-ornithine:2-oxo-acid aminotransferase [EC 2.6.1.13]) was investigated, and Bacillus sphaericus (IFO 3525) was found to have the highest activity of the enzyme, which was inducibly formed by addition of L-ornithine or L-arginine to the medium. L-Ornithine:alpha-ketoglutarate delta-aminotransferase, purified to homogeneity and crystallized from B. sphaericus, had a molecular weight of about 80,000 and consisted of two subunits identical in molecular weight (41,000) and in amino-terminal residue (threonine). The enzyme exhibited absorption maxima at 278,343, and 425 nm and contained 1 mol of pyridoxal 5'-phosphate per mol of enzyme. The formyl group of pyridoxal 5'-phosphate was bound through an aldimine linkage to the epsilon-amino group of a lysine residue of the protein. The enzyme-bound pyridoxal 5'-phosphate, absorbing at 425 nm, was released by incubation with phenylhydrazine to yield the catalytically inactive form. The inactive enzyme, which was reactivated by addition of pyridoxal 5'-phosphate, still had a 343-nm peak and contained 1 mol of a vitamin B6 compound. The holoenzyme showed positive circular dichroic bands at 340 and 425 nm, whereas the inactive form had no band at 425 nm. The enzyme was highly specific for L-ornithine and alpha-ketoglutarate and catalyzed delta-transamination between them to produce L-glutamate and L-glutamate-gamma-semialdehyde, which as spontaneously converted to delta 1-pyrroline-5-carboxylate. The enzyme activity was significantly affected by nonsubstrate amino acids, amines, and carbonyl reagents.
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In the course of cytoarchitectonic studies on the hypothalamus of the fowl, 6 cell masses which may be respectively considered as one nucleus, were newly found around the commissura anterior (CA). They were provisionally designated nuclei A-F in this study. In the frontal sections, nucleus A was a grape-like cell mass composed of the smallest round cells in the lateral preoptic area. Nuclei B and D were the most deeply stained cell masses showing round shapes. The former was located immediately rostral to the CA and consisted of cells oriented dorsoventralward, while the latter, situated dorsal to the CA, were composed of cells oriented rostrocaudalward. In contrast to the other 5 deeply stained and compact cell masses, nucleus C was the most poorly stained cell group. It was composed of two types of cells which were located around the margin of the CA. Under the CA, nucleus E was found to be the broadest cell mass composed of densely located cells. Further caudally, nucleus F was also found as a compact cell mass consisting of the poorly stained and densely located cells.
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The malignant ovarian cancer cells removed on operation were cultured and exposed to the anticancer drug (either 5-fluorouracil or mitomycin C) for 30 minutes or 24 hours respectively. The activity of the LDH and LDH isozyme in the culture medium was measured. Also the activity of the LDH and its isozyme was determined in the patients undergoing chemotherapy with either 5-fluorouracil or mitomycin C. The results are summarized as follows: 1) The LDH isozyme pattern of the culture medium prior to exposure of malignant cells to the anticancer drugs was classified into 2 types i.e., M type which is characterized by a predominance of LDH4,5 (referred hereinafter to as group M) and H type with a predominance of LDH1,2 (referred to as group H). 2) Of 11 cases studied, 7 were classified as group M and 4 were categorized as group H. there was no distinct relationship between histological type and LDH isozyme pattern. 3) In the group with exposure to anticancer drugs the total LDH activity in both group H and group M was lower than in the control group. Control specimens in group H showed increased total LDH activity. 4) The H/M ratio based on subunits of LDH isozyme was virtually unchanged by exposure to anticancer drugs in group M, while rapidly lowered by the same treatment in group H. 5) The death rate of malignant cells as estimated by dye exclusion methods was higher with exposure to anticancer drugs than without it. 6) The serum LDH was more markedly lowered after treatment in group H than in group M. However, there was no substantial difference between the two groups in M/H ratio before and after treatment.
We examined the relationship between body weight and ossification of coccygeal vertebrae in normal full-term fetuses of mice and rats to reliably evaluate fetal growth retardation in teratological tests. Correlation coefficients between body weight and number of ossified coccygeal vertebrae were positive in mice and rats. However, the coefficients were variable between groups and were not statistically significant in some groups. Averages of body weight and ossified coccygeal vertebrae were variable in the normal fetuses. However, the coefficient of variation in each group was nearly constant, and the component of variance between groups (sigma 1(2)) was small as compared with that within groups (sigma 0(2)). Therefore, the relationship between low body weight and retardation of ossification observed in teratological experiments may be evaluated by measuring relative differences of body weight and ossification between the treated group and the control group with the variance within groups (sigma 0) as a scale.
1. Effects of 4-pentenoic acid (4-PA), an inhibitor of fatty acid oxidation, on renal fatty acids (FFA) were investigated using mongrel dogs, and the results compared with findings in the case of furosemide. 2. Continuous infusion of 4-PA at a rate of 0.66 mumoles/kg.min into the renal artery resulted in a marked reduction of glomerular filtration rate after 45 min. Sodium reabsorption rate tended to decrease at 30 min and a significant decrease was seen after 45 min. With decrease in the renal sodium reabsorption rate, the urine flow increased about 3 times, and there was a marked natriuresis. 3. Concentrations of individual FFA in the arterial and renal venous plasma were determined by gas-liquid chromatographic analysis. In the control period, data from 25 dogs showed renal uptake of palmitic, stearic, oleic, and linoleic acids to be approximately 40, 15, 25, and 10 nmoles/g.min, respectively, and the uptake of palmitic and oleic acids was depressed during the natriuresis following administration of 4-PA and furosemide. 4. These results suggest that fatty acids play an important role in the energy supply in renal tubular sodium transport.
The effects of niceritrol, a nicotinic acid derivative, on the levels of HDL-cholesterol (HDL-Ch) and a mixture of VLDL- and LDL-Ch (VLDL- + LDL-Ch) were studied in hyperlipidemic patients. Serum total cholesterol (sTC) and serum triglyceride (sTG) were significantly reduced during niceritrol administration. Lipoprotein electrophoresis showed that niceritrol increased the alpha:beta ratio. HDL-Ch showed a significant increase of 12.5% by the 16th week of therapy. This increase was more marked in patients with lower pre-treatment HDL-Ch levels and significant in patients whose pre-treatment sTG levels were in excess of 200 mg/dl. Females displayed higher pre-treatment HDL-Ch levels (38.5 mg/dl) than males (30.6 mg/dl). However, niceritrol increased HDL-Ch significantly in both groups. At 16 weeks, the VLDL- + LDL-Ch level showed a significant decrease of 9.2%; the HDL-Ch:VLDL + LDL-Ch and HDL-CH:sTC ratios were significantly increased throughout niceritrol administration. Niceritrol is thought to be effective in preventing the development and progression of atherosclerosis because it raises the level of anti-atherogenic HDL-Ch and lowers the level of atherogenic VLDL- + LDL-Ch.
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The subarachnoid space, the chorioid plexus and the arachnoid villi are microscopically studied in 60 normal human embryos and in 3 abnormal human embryos with rhombencephaloschisis and cervical myeloschisis. The subarachnoid space has been generally considered to be developed by outflow of cerebrospinal fluid (CSF) of the choroid-plexus origin from the IVth ventricle. This generally accepted concept does not meet with our findings: (1) cavity formation in the meninx primitiva is seen before appearance of the choroid plexus; (2) the primitive subarachnoid space is developed earlier in the prepontine region than in the area dorsal to the rhombic roof, and (3) the primitive subarachnoid space is formed in the embryos with dysraphism where the perineural subarachnoid space is separated from the ventricles. Apparently the embryonic pattern of CSF circulation should be much different from the generally believed pattern of adult, since the arachnoid villi are absent in the embryos and the ability of production of CSF in the embryonic choroid plexus is questionable. It is suggested that such embryonic pattern of CSF production and absorption may partly persist in adult human being.
Twenty-two cockerels were adenohypophysectomized by the improved transbuccal approach to observe histological changes in the testis during 60 postoperative days. Total adenohypophysectomy induced a collapse of spermatogenic cells and a decrease in the diameter of seminiferous tubules, accompanied by a rapid decrease in testicular weight. The patterns of degeneration of various spermatogenic cells were different from each other. Spermatozoa and spermatids were detached from the epithelium by day 5, spermatocytes by day 10, and more than half of spermatogonia by day 20 after the operation. Sertoli cells reduced their cytoplasmic processes on day 3 but still retained their height to sustain an indented form of epithelium between days 3 and 10, when most spermatogenic cells were disengaged from the epithelium. Sertoli cells were never sloughed off into the lumen. On and after day 20, seminiferous epithelium was monolayered, consisting of atrophied Sertoli cells with small sized nuclei and spermatogonia. Interstitial cells tended to agglomere maximum on day 60. Interstitium occupied more than 30% of estimated total volume of testis from day 20 onward. According to the observation on day 30, the degree of degeneration of seminiferous tubules in later stages depended on the location within the testis. The network of cytoplasmic processes of Sertoli cells persisted in the central but not in the peripheral region.